1. Institute of Protein Research, Pushchino, Moscow Region, Russia 2. Institute of Cell Biophysics, Pushchino, Moscow Region, Russia 3. Institute of Protein Research, Pushchino, Moscow Region, Russia; State Scientific Center of Applied Microbiology and biotechnology, Village Obolensk, Moscow Region, Serpukhov District, Russia
TA characteristic feature of amyloid structures is polymorphism. The study of amyloid structures and their formation process was carried out for synthetic and recombinant Ab(1-40) and Ab(1-42) peptide preparations. In the study of these peptides, we recognized fibrils of different morphologies. We observed fibrillar formations in the form of single fibrils, ribbons, bundles, bunches, and clusters. Polymorphism of fibrils was observed not only when the environmental conditions changed, but under the same conditions and this was a common characteristics of all amyloid formations. Fibrils of Ab(1-40) peptides tended to form aggregates of fibrils in the form of ribbons, while Ab(1-42) peptide under the same conditions polymerized in the form of rough fibrils of different diameters and tends to branch. We assume that the formation of fibrils of Ab(1-40) and Ab(1-42) peptides occurs according to a simplified scheme: a destabilized monomer ® a ring oligomer ® a mature fibril consisting of ring oligomers. Proceeding from the proposition that the ring oligomer is the main building block of amyloid fibril (similar to the cell in the body), it is easy to explain fibril polymorphism, as well as fragmentation of mature fibrils under various external influences, branching and irregularity of diameter (surface roughness) of fibrils. One aspect of the study of amyloidogenesis is the determination of the regions of the protein chain forming the core of the amyloid fibril. We theoretically predicted amyloidogenic regions for two isoforms of Ab peptides capable of forming an amyloid structure: 16-21 and 32-36 residues. Using the method of tandem mass spectrometry, these regions were determined experimentally. It was shown that the regions of Ab(1-40) peptide from 16 to 22 and from 28 to 40 residues were resistant to the action of proteases, i.e. its formed the core of the amyloid fibril. For Ab(1-42) peptide the whole sequence is not available for the action of proteases, which indicates a different way of associating ring oligomers in the formation of fibrils. Based on electron microscopy and mass spectrometry data we proposed a molecular model of the fibril formed by Ab(1-40) and Ab(1-42) peptides.
Selivanova O.M., Rogachevsky V.V., Syrin A.K., Galzitskaya O.V. (2018) Molecular mechanism of amyloid formation by Ab peptide: review of own works. Biomeditsinskaya Khimiya, 64(1), 94-109.
Selivanova O.M. et al. Molecular mechanism of amyloid formation by Ab peptide: review of own works // Biomeditsinskaya Khimiya. - 2018. - V. 64. -N 1. - P. 94-109.
Selivanova O.M. et al., "Molecular mechanism of amyloid formation by Ab peptide: review of own works." Biomeditsinskaya Khimiya 64.1 (2018): 94-109.
Selivanova, O. M., Rogachevsky, V. V., Syrin, A. K., Galzitskaya, O. V. (2018). Molecular mechanism of amyloid formation by Ab peptide: review of own works. Biomeditsinskaya Khimiya, 64(1), 94-109.
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